Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis

Motohide Uemura; Hiroaki Kikukawa; Yasuhiro Hashimoto; Hiroji Uemura; Atsushi Mizokami; Masashi Kato; Hisashi Matsushima; Takeo Kosaka; Motonobu Nakamura; Satoshi Fukasawa; Matthew R. Smith; Bertrand Tombal; Maha Hussain; Fred Saad; Karim Fizazi; Cora N. Sternberg; E. David Crawford; Haruka Kakiuchi; Masanao Akiyama; Rui Li; Iris Kuss; Heikki Joensuu; Hiroyoshi Suzuki

doi:10.1002/cam4.70029

Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis

Motohide Uemura^*, Hiroaki Kikukawa, Yasuhiro Hashimoto, Hiroji Uemura, Atsushi Mizokami, Masashi Kato, Hisashi Matsushima, Takeo Kosaka, Motonobu Nakamura, Satoshi Fukasawa, Matthew R. Smith, Bertrand Tombal, Maha Hussain, Fred Saad, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Haruka Kakiuchi, Masanao Akiyama, Rui LiIris Kuss, Heikki Joensuu, Hiroyoshi Suzuki

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

Abstract

Background: In the global ARASENS study (NCT02799602), darolutamide plus androgen-deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57–0.80; p < 0.0001), with a favorable safety profile in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants. Methods: Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival. Results: The Japanese subgroup comprised 148 patients (darolutamide 63, placebo 85). In the Japanese versus overall population, more patients were aged ≥75 years (darolutamide/placebo 35%/22% vs. 16%/17%) and had body mass index <25 kg/m² (78%/79% vs. 46%/43%), The ECOG performance status 0 (92%/88% vs. 72%/71%), de novo mHSPC (95%/97% vs. 86%/87%), and Gleason score ≥8 (94%/92% vs. 78%/79%). Median treatment duration was 43.3/15.4 months for darolutamide/placebo. The overall survival HR for darolutamide versus placebo was 0.91 (95% CI 0.50–1.64), despite 85% of patients in the placebo group receiving subsequent life-prolonging therapy. Darolutamide prolonged time to castration-resistant prostate cancer (HR 0.31; 95% CI 0.17–0.55). Treatment-emergent adverse event incidences were generally similar between groups. Adverse events known to be associated with docetaxel (e.g., neutropenia) were more frequent in the Japanese versus overall population. Conclusion: In conclusion, efficacy outcomes showed positive trends for darolutamide plus ADT and docetaxel in Japanese patients with mHSPC, consistent with the overall population, despite higher risk factors. The combination was well tolerated, with no new safety signals in Japanese patients.

Original language	English (US)
Article number	e70029
Journal	Cancer medicine
Volume	13
Issue number	21
DOIs	https://doi.org/10.1002/cam4.70029
State	Published - Nov 2024

Funding

Medical writing support was provided by Sara Black, ISMPP CMPP\u2122, of Luna, OPEN Health Communications, London, UK, and funded by Bayer HealthCare Pharmaceuticals, in accordance with Good Publication Practice (GPP) guidelines (www.ismp.org/gpp-2022). The ARASENS study was supported by Bayer and Orion Pharma.

Keywords

Japanese
darolutamide
efficacy
metastatic hormone-sensitive prostate cancer
safety

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cam4.70029

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Uemura, M., Kikukawa, H., Hashimoto, Y., Uemura, H., Mizokami, A., Kato, M., Matsushima, H., Kosaka, T., Nakamura, M., Fukasawa, S., Smith, M. R., Tombal, B., Hussain, M., Saad, F., Fizazi, K., Sternberg, C. N., Crawford, E. D., Kakiuchi, H., Akiyama, M., ... Suzuki, H. (2024). Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis. Cancer medicine, 13(21), Article e70029. https://doi.org/10.1002/cam4.70029

@article{0292f937b65c4bbdb14991f273946ed5,

title = "Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis",

abstract = "Background: In the global ARASENS study (NCT02799602), darolutamide plus androgen-deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57–0.80; p < 0.0001), with a favorable safety profile in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants. Methods: Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival. Results: The Japanese subgroup comprised 148 patients (darolutamide 63, placebo 85). In the Japanese versus overall population, more patients were aged ≥75 years (darolutamide/placebo 35%/22% vs. 16%/17%) and had body mass index <25 kg/m2 (78%/79% vs. 46%/43%), The ECOG performance status 0 (92%/88% vs. 72%/71%), de novo mHSPC (95%/97% vs. 86%/87%), and Gleason score ≥8 (94%/92% vs. 78%/79%). Median treatment duration was 43.3/15.4 months for darolutamide/placebo. The overall survival HR for darolutamide versus placebo was 0.91 (95% CI 0.50–1.64), despite 85% of patients in the placebo group receiving subsequent life-prolonging therapy. Darolutamide prolonged time to castration-resistant prostate cancer (HR 0.31; 95% CI 0.17–0.55). Treatment-emergent adverse event incidences were generally similar between groups. Adverse events known to be associated with docetaxel (e.g., neutropenia) were more frequent in the Japanese versus overall population. Conclusion: In conclusion, efficacy outcomes showed positive trends for darolutamide plus ADT and docetaxel in Japanese patients with mHSPC, consistent with the overall population, despite higher risk factors. The combination was well tolerated, with no new safety signals in Japanese patients.",

keywords = "Japanese, darolutamide, efficacy, metastatic hormone-sensitive prostate cancer, safety",

author = "Motohide Uemura and Hiroaki Kikukawa and Yasuhiro Hashimoto and Hiroji Uemura and Atsushi Mizokami and Masashi Kato and Hisashi Matsushima and Takeo Kosaka and Motonobu Nakamura and Satoshi Fukasawa and Smith, {Matthew R.} and Bertrand Tombal and Maha Hussain and Fred Saad and Karim Fizazi and Sternberg, {Cora N.} and Crawford, {E. David} and Haruka Kakiuchi and Masanao Akiyama and Rui Li and Iris Kuss and Heikki Joensuu and Hiroyoshi Suzuki",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.",

year = "2024",

month = nov,

doi = "10.1002/cam4.70029",

language = "English (US)",

volume = "13",

journal = "Cancer medicine",

issn = "2045-7634",

publisher = "John Wiley and Sons Inc.",

number = "21",

}

Uemura, M, Kikukawa, H, Hashimoto, Y, Uemura, H, Mizokami, A, Kato, M, Matsushima, H, Kosaka, T, Nakamura, M, Fukasawa, S, Smith, MR, Tombal, B, Hussain, M, Saad, F, Fizazi, K, Sternberg, CN, Crawford, ED, Kakiuchi, H, Akiyama, M, Li, R, Kuss, I, Joensuu, H & Suzuki, H 2024, 'Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis', Cancer medicine, vol. 13, no. 21, e70029. https://doi.org/10.1002/cam4.70029

TY - JOUR

T1 - Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer

T2 - Phase 3 ARASENS subgroup analysis

AU - Uemura, Motohide

AU - Kikukawa, Hiroaki

AU - Hashimoto, Yasuhiro

AU - Uemura, Hiroji

AU - Mizokami, Atsushi

AU - Kato, Masashi

AU - Matsushima, Hisashi

AU - Kosaka, Takeo

AU - Nakamura, Motonobu

AU - Fukasawa, Satoshi

AU - Smith, Matthew R.

AU - Tombal, Bertrand

AU - Hussain, Maha

AU - Saad, Fred

AU - Fizazi, Karim

AU - Sternberg, Cora N.

AU - Crawford, E. David

AU - Kakiuchi, Haruka

AU - Akiyama, Masanao

AU - Li, Rui

AU - Kuss, Iris

AU - Joensuu, Heikki

AU - Suzuki, Hiroyoshi

PY - 2024/11

Y1 - 2024/11

N2 - Background: In the global ARASENS study (NCT02799602), darolutamide plus androgen-deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57–0.80; p < 0.0001), with a favorable safety profile in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants. Methods: Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival. Results: The Japanese subgroup comprised 148 patients (darolutamide 63, placebo 85). In the Japanese versus overall population, more patients were aged ≥75 years (darolutamide/placebo 35%/22% vs. 16%/17%) and had body mass index <25 kg/m2 (78%/79% vs. 46%/43%), The ECOG performance status 0 (92%/88% vs. 72%/71%), de novo mHSPC (95%/97% vs. 86%/87%), and Gleason score ≥8 (94%/92% vs. 78%/79%). Median treatment duration was 43.3/15.4 months for darolutamide/placebo. The overall survival HR for darolutamide versus placebo was 0.91 (95% CI 0.50–1.64), despite 85% of patients in the placebo group receiving subsequent life-prolonging therapy. Darolutamide prolonged time to castration-resistant prostate cancer (HR 0.31; 95% CI 0.17–0.55). Treatment-emergent adverse event incidences were generally similar between groups. Adverse events known to be associated with docetaxel (e.g., neutropenia) were more frequent in the Japanese versus overall population. Conclusion: In conclusion, efficacy outcomes showed positive trends for darolutamide plus ADT and docetaxel in Japanese patients with mHSPC, consistent with the overall population, despite higher risk factors. The combination was well tolerated, with no new safety signals in Japanese patients.

AB - Background: In the global ARASENS study (NCT02799602), darolutamide plus androgen-deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57–0.80; p < 0.0001), with a favorable safety profile in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants. Methods: Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival. Results: The Japanese subgroup comprised 148 patients (darolutamide 63, placebo 85). In the Japanese versus overall population, more patients were aged ≥75 years (darolutamide/placebo 35%/22% vs. 16%/17%) and had body mass index <25 kg/m2 (78%/79% vs. 46%/43%), The ECOG performance status 0 (92%/88% vs. 72%/71%), de novo mHSPC (95%/97% vs. 86%/87%), and Gleason score ≥8 (94%/92% vs. 78%/79%). Median treatment duration was 43.3/15.4 months for darolutamide/placebo. The overall survival HR for darolutamide versus placebo was 0.91 (95% CI 0.50–1.64), despite 85% of patients in the placebo group receiving subsequent life-prolonging therapy. Darolutamide prolonged time to castration-resistant prostate cancer (HR 0.31; 95% CI 0.17–0.55). Treatment-emergent adverse event incidences were generally similar between groups. Adverse events known to be associated with docetaxel (e.g., neutropenia) were more frequent in the Japanese versus overall population. Conclusion: In conclusion, efficacy outcomes showed positive trends for darolutamide plus ADT and docetaxel in Japanese patients with mHSPC, consistent with the overall population, despite higher risk factors. The combination was well tolerated, with no new safety signals in Japanese patients.

KW - Japanese

KW - darolutamide

KW - efficacy

KW - metastatic hormone-sensitive prostate cancer

KW - safety

UR - http://www.scopus.com/inward/record.url?scp=85208787007&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85208787007&partnerID=8YFLogxK

U2 - 10.1002/cam4.70029

DO - 10.1002/cam4.70029

M3 - Article

C2 - 39527466

AN - SCOPUS:85208787007

SN - 2045-7634

VL - 13

JO - Cancer medicine

JF - Cancer medicine

IS - 21

M1 - e70029

ER -

Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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